Stability of genetic polymorphism in host-parasite interactions

Allelic diversity is common at host loci involved in parasite recognition, such as the major histocompatibility complex in vertebrates or gene-for-gene relationships in plants, and in corresponding loci encoding antigenic molecules in parasites. Diverse factors have been proposed in models to account for genetic polymorphism in host-parasite recognition. Here, a simple but general theory of host-parasite coevolution is developed. Coevolution implies the existence of indirect frequency-dependent selection (FDS), because natural selection on the host depends on the frequency of a parasite gene, and vice versa. It is shown that polymorphism can be maintained in both organisms only if there is negative, direct FDS, such that the strength of natural selection for the host resistance allele, the parasite virulence allele or both declines with increasing frequency of that allele itself. This condition may be fulfilled if the parasite has more than one generation in the same host individual, a feature which is common to most diseases. It is argued that the general theory encompasses almost all factors previously proposed to account for polymorphism at corresponding host and parasite loci, including those controlling gene-for-gene interactions.     

Host-parasite coevolution in a multilocus gene-for-gene system.

This paper examines a mathematical model for the coevolution of parasite virulence and host resistance under a multilocus gene-for-gene interaction. The degrees of parasite virulence and host resistance show coevolutionary cycles for sufficiently small costs of virulence and resistance. Besides these coevolutionary cycles of a longer period, multilocus genotype frequencies show complex fluctuations over shorter periods. All multilocus genotypes are maintained within host and parasite classes having the same number of resistant/virulent alleles and their frequencies fluctuate with approximately equally displaced phases. If either the cost of virulence or the number of resistance loci is larger then a threshold, the host maintains the static polymorphism of singly (or doubly or more, depending on the cost of resistance) resistant genotypes and the parasite remains universally avirulent. In other words, host polymorphism can prevent the invasion of any virulent strain in the parasite. Thus, although assuming an empirically common type of asymmetrical gene-for-gene interaction, both host and parasite populations can maintain polymorphism in each locus and retain complex fluctuations. Implications for the red queen hypothesis of the evolution of sex and the control of multiple drug resistance are discussed.     

Ecological genetics of the Bromus tectorum (Poaceae)-Ustilago bullata (Ustilaginaceae) pathosystem: A role for frequency-dependent selection?

? Premise of the study: Evolutionary processes that maintain genetic diversity in plants are likely to include selection imposed by pathogens. Negative frequency-dependent selection is a mechanism for maintenance of resistance polymorphism in plant-pathogen interactions. We explored whether such selection operates in the Bromus tectorum-Ustilago bullata pathosystem. Gene-for-gene relationships between resistance and avirulence loci have been demonstrated for this pathosystem. ? Methods: We used molecular markers and cross-inoculation trials to learn whether the SSR genotypes of the host exhibited resistance to co-occurring pathogen races, whether host genotypes within a population had equal disease probability, and whether a common resistance locus and its corresponding avirulence locus exhibited predicted allele frequency changes during an epidemic. ? Key results: Five of six putative resistance loci that conferred resistance to co-occurring pathogen races occurred in common host SSR genotypes. Some common genotypes within populations were more likely to be diseased than others, and genotype frequencies sometimes changed across years in patterns consistent with frequency-dependent selection. Observed changes in frequency of resistance and virulence alleles during an epidemic provided further support, but evidence was inconclusive. ? Conclusions: Frequency-dependent selection may operate at endemic disease levels in this pathosystem, but is difficult to detect because many susceptible plants escape infection. Most pathogen isolates were virulent on most host genotypes, minimizing the apparent importance of frequency-dependent selection even during epidemics.     

Heterogeneous selection promotes maintenance of polymorphism in host–parasite interactions

Polymorphism in loci affecting host resistance and parasite virulence is characteristic for nearly all species and this genetic variation is considered to have profound consequences for the patterns of disease incidence, prevalence and evolution. The gene-for-gene (GFG) system is a well-characterized genetic interaction of host recognition and parasite antigenic loci for a wide range of plant-parasite interactions. Long-term maintenance of polymorphism in GFG systems has remained puzzling for both theoreticians and empiricists. Traditionally this diversity has been explained by tradeoffs with other life-history traits closely linked with fitness, yet empirical evidence for such costs has remained mixed. Here we argue that incorporating simple ecological reality – spatial structuring and gradient of environmental conditions – into host–parasite research will help us understand how polymorphism is maintained. While environmental conditions (biotic and abiotic factors) have been studied in depth in plant pathology for their influence on disease severity and plant yield, they have been rarely set into an evolutionary framework. We briefly review recent data on natural plant–parasite metapopulations and theoretical models moving from single population models towards metapopulation theory to reveal in just how many ways spatial structuring may affect the coevolutionary process. We clarify also how spatially heterogeneous selection, through G×E (or G×G×E) interactions, may be particularly important for natural host–parasite interactions and suggest that this provides the unifying ground upon which future theoretical and empirical work should be build on.     

The evolution of parasite virulence, superinfection, and host resistance

We analyze the evolutionary consequences of host resistance (the ability to decrease the probability of being infected by parasites) for the evolution of parasite virulence (the deleterious effect of a parasite on its host). When only single infections occur, host resistance does not affect the evolution of parasite virulence. However, when superinfections occur, resistance tends to decrease the evolutionarily stable (ES) level of parasite virulence. We first study a simple model in which the host does not coevolve with the parasite (i.e., the frequency of resistant hosts is independent of the parasite). We show that a higher proportion of resistant host decreases the ES level of parasite virulence. Higher levels of the efficiency of host resistance, however, do not always decrease the ES parasite virulence. The implications of these results for virulence management (evolutionary consequences of public health policies) are discussed. Second, we analyze the case where host resistance is allowed to coevolve with parasite virulence using the classical gene-for-gene (GFG) model of host-parasite interaction. It is shown that GFG coevolution leads to lower parasite virulence (in comparison with a fully susceptible host population). The model clarifies and relates the different components of the cost of parasitism: infectivity (ability to infect the host) and virulence (deleterious effect) in an evolutionary perspective.     

Host-parasite interactions and the evolution of gene expression

Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and parasite infection. Our results reveal the striking yet intuitive conclusion that gene expression should evolve along very different trajectories in the two interacting species. Specifically, host resistance loci should frequently evolve to co-express alleles, whereas parasite infection loci should evolve to express only a single allele. This result arises because hosts that co-express resistance alleles are able to recognize and clear a greater diversity of parasite genotypes. By the same token, parasites that co-express antigen or elicitor alleles are more likely to be recognized and cleared by the host, and this favours the expression of only a single allele. Our model provides testable predictions that can help interpret accumulating data on expression levels for genes relevant to host-parasite interactions.     

Host–Parasite Interactions and the Evolution of Gene Expression

Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and parasite infection. Our results reveal the striking yet intuitive conclusion that gene expression should evolve along very different trajectories in the two interacting species. Specifically, host resistance loci should frequently evolve to co-express alleles, whereas parasite infection loci should evolve to express only a single allele. This result arises because hosts that co-express resistance alleles are able to recognize and clear a greater diversity of parasite genotypes. By the same token, parasites that co-express antigen or elicitor alleles are more likely to be recognized and cleared by the host, and this favours the expression of only a single allele. Our model provides testable predictions that can help interpret accumulating data on expression levels for genes relevant to host−parasite interactions.     

Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata

Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.     

THE COEVOLUTIONARY IMPLICATIONS OF HOST TOLERANCE

Host tolerance to infectious disease, whereby hosts do not directly “fight” parasites but instead ameliorate the damage caused, is an important defense mechanism in both plants and animals. Because tolerance to parasite virulence may lead to higher prevalence of disease in a population, evolutionary theory tells us that while the spread of resistance genes will result in negative frequency dependence and the potential for diversification, the evolution of tolerance is instead likely to result in fixation. However, our understanding of the broader implications of tolerance is limited by a lack of fully coevolutionary theory. Here we examine the coevolution of tolerance across a comprehensive range of classic coevolutionary host–parasite frameworks, including equivalents of gene‐for‐gene and matching allele and evolutionary invasion models. Our models show that the coevolution of host tolerance and parasite virulence does not lead to the generation and maintenance of diversity through either static polymorphisms or through “Red‐queen” cycles. Coevolution of tolerance may however lead to multiple stable states leading to sudden shifts in parasite impacts on host health. More broadly, we emphasize that tolerance may change host–parasite interactions from antagonistic to a form of “apparent commensalism,” but may also lead to the evolution of parasites that are highly virulent in nontolerant hosts.     

Parasite-mediated selection drives an immunogenetic trade-off in plains zebras (Equus quagga)

Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite ‘susceptibility alleles’ were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.     

Pathogen resistance and genetic variation at MHC loci

Abstract.— Balancing selection in the form of heterozygote advantage, frequency-dependent selection, or selection that varies in time and/or space, has been proposed to explain the high variation at major histocompatibility complex (MHC) genes. Here the effect of variation of the presence and absence of pathogens over time on genetic variation at multiallelic loci is examined. In the basic model, resistance to each pathogen is conferred by a given allele, and this allele is assumed to be dominant. Given that s is the selective disadvantage for homozygotes (and heterozygotes) without the resistance allele and the proportion of generations, which a pathogen is present, is e , fitnesses for homozygotes become (1 — s )^(n-1)e and the fitnesses for heterozygotes become (1 — s )^(n-2)e, where n is the number of alleles. In this situation, the conditions for a stable, multiallelic polymorphism are met even though there is no intrinsic heterozygote advantage. The distribution of allele frequencies and consequently heterozygosity are a function of the autocorrelation of the presence of the pathogen in subsequent generations. When there is a positive autocorrelation over generations, the observed heterozygosity is reduced. In addition, the effects of lower levels of selection and dominance and the influence of genetic drift were examined. These effects were compared to the observed heterozygosity for two MHC genes in several South American Indian samples. Overall, resistance conferred by specific alleles to temporally variable pathogens may contribute to the observed polymorphism at MHC genes and other similar host defense loci.     

The effect of host heterogeneity and parasite intragenomic interactions on parasite population structure

Understanding the processes that shape the genetic structure of parasite populations and the functional consequences of different parasite genotypes is critical for our ability to predict how an infection can spread through a host population and for the design of effective vaccines to combat infection and disease. Here, we examine how the genetic structure of parasite populations responds to host genetic heterogeneity. We consider the well-characterized molecular specificity of major histocompatibility complex binding of antigenic peptides to derive deterministic and stochastic models. We use these models to ask, firstly, what conditions favour the evolution of generalist parasite genotypes versus specialist parasite genotypes? Secondly, can parasite genotypes coexist in a population? We find that intragenomic interactions between parasite loci encoding antigenic peptides are pivotal in determining the outcome of evolution. Where parasite loci interact synergistically (i.e. the recognition of additional antigenic peptides has a disproportionately large effect on parasite fitness), generalist parasite genotypes are favoured. Where parasite loci act multiplicatively (have independent effects on fitness) or antagonistically (have diminishing effects on parasite fitness), specialist parasite genotypes are favoured. A key finding is that polymorphism is not stable and that, with respect to functionally important antigenic peptides, parasite populations are dominated by a single genotype.     

Reliability of statistical analyses for estimating relative specificity in quantitative resistance in a model host-pathogen system

Summary The reliability of analyses of variance for evaluating host cultivar x pathogen isolate specificity in resistance controlled by polygenes with additive effects was tested with combinations of hypothetical host and pathogen genotypes in a model system. In each test, varying numbers of host and pathogen genotypes were combined in all combinations, the resulting disease severities were calculated according to the model, and those data were subjected to analysis of variance. The percentage of total variance accounted for by host x pathogen interaction decreased with increasing numbers of host and pathogen genotypes per test. Simulated selection for virulence among randomly generated pathogen genotypes increased the percentage of variance attributable to host x pathogen genotype interaction, but simulated selection for resistance among host genotypes decreased it. The percentage of variance accounted for by interaction was greatest when selection of resistant host genotypes was followed by selection of the most virulent pathogen genotype on each selected host genotype. When gene frequencies were varied in the model, the interaction variance was greatest at low frequencies of resistance genes and high frequencies of virulence genes, but the number of matches between genes for specific virulence and specific resistance was greatest for high frequencies of both resistance and virulence genes. A simplified method of analysis was developed to estimate the amount of specific resistance in a set of host genotypes inoculated in all combinations with a set of pathogen genotypes. This method, based on the variance of disease severity adjusted to remove general virulence, proved consistently accurate with varying numbers of genotypes in the set, varying numbers of loci for resistance and virulence, and varying frequencies of genes for resistance and virulence. The variance method is of comparable accuracy and is much simpler than the previously proposed methods based on regression analysis. Simulated selection for resistance in the host and for virulence in the pathogen population increased the accuracy of both the variance method and the regression method.     

Red queen meets Santa Rosalia: arms races and the evolution of host specialization in organisms with parasitic lifestyles

I argue that nonequilibrium allele frequency dynamics due to coevolution can drive the evolution of specialized host races in parasites capable of host choice-for example, herbivorous insects or parasitoids. The proposed mechanism does not require genetic trade-offs in performance on different host species. It is based on the premise that the ability of the parasite to overcome the resistance of different host species is to a large degree genetically independent-that is, controlled by different loci. The intuitive rationale is that the genetic lineage of a parasite that evolves host preference becomes more consistently exposed to selection for performance on its preferred host. Such a choosy lineage can thus coevolve faster in response to evolving host defenses than a generalist lineage distributed among several host species. Given genetic variation in host preference, an initially generalist parasite population evolves toward specialized host races, each choosing one host species. This idea is supported by a series of multilocus models of coevolution between a parasite and two host species, in which the parasite virulence on each host is affected by a different set of loci and an additional locus or two loci control host choice.     

The genetic architecture of disease resistance in plants and the maintenance of recombination by parasites

Parasites represent strong selection on host populations because they are ubiquitous and can drastically reduce host fitness. It has been hypothesized that parasite selection could explain the widespread occurrence of recombination because it is a coevolving force that favours new genetic combinations in the host. A review of deterministic models for the maintenance of recombination reveals that for recombination to be favoured, multiple genes that interact with each other must be under selection. To evaluate whether parasite selection can explain the maintenance of recombination, we review 85 studies that investigated the genetic architecture of plant disease resistance and discuss whether they conform to the requirements that emerge from theoretical models. General characteristics of disease resistance in plants and problems in evaluating resistance experimentally are also discussed. We found strong evidence that disease resistance in plants is determined by multiple loci. Furthermore, in most cases where loci were tested for interactions, epistasis between loci that affect resistance was found. However, we found weak support for the idea that specific allelic combinations determine resistance to different host genotypes and there was little data on whether epistasis between resistance genes is negative or positive. Thus, the current data indicate that it is possible that parasite selection can favour recombination, but more studies in natural populations that specifically address the nature of the interactions between resistance genes are necessary. The data summarized here suggest that disease resistance is a complex trait and that environmental effects and fitness trade-offs should be considered in future models of the coevolutionary dynamics of host and parasites.     

Signals of demographic expansion in Drosophila virilis

Background

The antagonistic co-evolution of hosts and their parasites is considered to be a potential driving force in maintaining host genetic variation including sexual reproduction and recombination. The examination of this hypothesis calls for information about the genetic basis of host-parasite interactions – such as how many genes are involved, how big an effect these genes have and whether there is epistasis between loci. We here examine the genetic architecture of quantitative resistance in animal and plant hosts by concatenating published studies that have identified quantitative trait loci (QTL) for host resistance in animals and plants.

Results

Collectively, these studies show that host resistance is affected by few loci. We particularly show that additional epistatic interactions, especially between loci on different chromosomes, explain a majority of the effects. Furthermore, we find that when experiments are repeated using different host or parasite genotypes under otherwise identical conditions, the underlying genetic architecture of host resistance can vary dramatically – that is, involves different QTLs and epistatic interactions. QTLs and epistatic loci vary much less when host and parasite types remain the same but experiments are repeated in different environments.

Conclusion

This pattern of variability of the genetic architecture is predicted by strong interactions between genotypes and corroborates the prevalence of varying host-parasite combinations over varying environmental conditions. Moreover, epistasis is a major determinant of phenotypic variance for host resistance. Because epistasis seems to occur predominantly between, rather than within, chromosomes, segregation and chromosome number rather than recombination via cross-over should be the major elements affecting adaptive change in host resistance.     

Disease, frequency-dependent selection, and genetic polymorphisms: experiments with stripe rust and wheat

Abstract.— Pathogens have the potential to maintain genetic polymorphisms by creating frequency-dependent selection on their host. This can occur when a rare host genotype is less likely to be attacked by a pathogen (frequency-dependent disease attack) and has higher fitness at low frequency (negative frequency-dependent selection). In this study, we used wheat genotypes that were susceptible to different races of the pathogen Puccinia striiformis to test whether disease created frequency-selection on its host and whether such selection could maintain polymorphisms for resistance genes in the wheat populations. Four different two-way mixtures of wheat genotypes were planted at different frequencies in both the presence and absence of disease. Disease created frequency-dependent selection on its host in some populations. Unknown factors other than disease also created frequency-dependent selection in this system because, in some instances, rare genotype advantage was observed in the absence of disease. Although the pathogen created frequency-dependent selection on its host, this selection was not sufficient to maintain genetic polymorphism in the host populations. In all cases where frequency-dependent selection occurred only in the diseased plots, one of the two genotypes was predicted to dominate in the population and the same genotype was predicted to dominate in both the presence and absence of disease. Only in cases where frequency-dependent selection was not caused by disease was there evidence that genetic polymorphisms would be maintained in the population. The frequency-dependent selection described in this study is a consequence of epidemiological effects of disease and differs from the time-lagged frequency-dependent selection resulting from coevolution between hosts and parasites. The impact of this direct frequency-dependent selection on the maintenance of genetic polymorphisms in the host population is discussed.     

Coevolutionary genetics of plants and pathogens

Summary The genetic polymorphism maintained by host-pathogen coevolution is analysed in a multilocus model. The model assumes gene-for-gene interactions of the type commonly observed between host plants and their fungal pathogens. Unstable (epidemic) systems maintain more resistance genes, fewer virulence genes, and less overall genetic diversity than stable (endemic) diseases. The stability of the system depends primarily on demographic parameters, such as the pathogen's intrinsic rate of increase, rather than genetic parameters, such as the costs of resistance and virulence. At equilibrium the model predicts that the number of resistance alleles in each host plant follows a binomial distribution that depends on the cost to the pathogen for carrying virulence alleles. Similarly, the number of virulence alleles in each pathogen spore follows a binomial distribution that depends on one minus the cost to the host for carrying resistance alleles. Data from wild populations match the predicted binomial distributions.     

Host-parasite interactions for virulence and resistance in a malaria model system

A rich body of theory on the evolution of virulence (disease severity) attempts to predict the conditions that cause parasites to harm their hosts, and a central assumption to many of these models is that the relative virulence of pathogen strains is stable across a range of host types. In contrast, a largely nonoverlapping body of theory on coevolution assumes that the fitness effects of parasites on hosts is not stable across host genotype, but instead depends on host genotype by parasite genotype interactions. If such genetic interactions largely determine virulence, it becomes difficult to predict the strength and direction of selection on virulence. In this study, we tested for host-by-parasite interactions in a medically relevant vertebrate disease model: the rodent malaria parasite Plasmodium chabaudi in laboratory mice. We found that parasite and particularly host main effects explained most of the variance in virulence (anaemia and weight loss), resistance (parasite burden) and transmission potential. Host-by-parasite interactions were of limited influence, but nevertheless had significant effects. This raises the possibility that host heterogeneity may affect the rate of any parasite response to selection on virulence. This study of rodent malaria is one of the first tests for host-by-parasite interactions in any vertebrate disease; host-by-parasite interactions typical of those assumed in coevolutionary models were present, but were by no means pervasive.     

HOST–PARASITE GENETIC INTERACTIONS AND VIRULENCE-TRANSMISSION RELATIONSHIPS IN NATURAL POPULATIONS OF MONARCH BUTTERFLIES

Evolutionary models predict that parasite virulence (parasite-induced host mortality) can evolve as a consequence of natural selection operating on between-host parasite transmission. Two major assumptions are that virulence and transmission are genetically related and that the relative virulence and transmission of parasite genotypes remain similar across host genotypes. We conducted a cross-infection experiment using monarch butterflies and their protozoan parasites from two populations in eastern and western North America. We tested each of 10 host family lines against each of 18 parasite genotypes and measured virulence (host life span) and parasite transmission potential (spore load). Consistent with virulence evolution theory, we found a positive relationship between virulence and transmission across parasite genotypes. However, the absolute values of virulence and transmission differed among host family lines, as did the rank order of parasite clones along the virulence-transmission relationship. Population-level analyses showed that parasites from western North America caused higher infection levels and virulence, but there was no evidence of local adaptation of parasites on sympatric hosts. Collectively, our results suggest that host genotypes can affect the strength and direction of selection on virulence in natural populations, and that predicting virulence evolution may require building genotype-specific interactions into simpler trade-off models.